UNIVERSITY OF CAMBRIDGE: Targeted Therapies for High-risk Pediatric Brain Tumor Subtypes

Year of Grant: 2015

Location: United Kingdom


Every child with a brain tumor is unlikely to be cured unless we can develop therapies that target each specific tumor subtype. While each form of childhood brain tumor includes subtypes with radically different origins, biology and prognoses, however, many still receive largely the same combination of surgery, radiation and conventional chemotherapy.


This study is specifically designed to completely rethink and redesign the drug development pipeline for brain tumors. It will use a unified, preclinical-clinical platform that integrates the latest mouse modelling, drug screening, molecular biology, and multi-modality preclinical trials, to identify effective new treatments with maximum curative potential for three of the most lethal pediatric brain tumor subtypes: Group-3 medulloblastoma, C11orf95-RELA translocation positive ependymoma, and choroid plexus carcinoma.


The team will engage clinicians, cancer biologists and medicinal chemists at all stages of the process, engendering multidisciplinary debate to overcome three major hurdles that have impeded progress in the treatment of pediatric brain tumors: (i) a large proportion of childhood brain tumor deaths are caused by individually rare and biologically distinct subtypes that are not recognized as entities in current clinical practice; (ii) Selection of new treatments for pediatric brain tumors also does not account for these subtypes, but focuses on large, heterogeneous histologic tumor diagnoses, or extrapolates data from unrelated cancers; (iii) the existing preclinical pipeline for potential new pediatric brain tumor therapies fails to recapitulate the subtype and treatment of the human disease and therefore lacks predictive power in the clinic.


By employing accurate mouse models of defined brain tumor subtypes in a comprehensive series of multi-platform studies to identify subtype-specific drug targets from the outset, the researchers aims to create a new roadmap to direct novel therapies from the lab to the clinic. With the combination of neurosurgical, radiation and chemotherapy trials, the team also hopes to set a new standard in preclinical drug development of pediatric brain tumors and other cancers.